Company Expects to Present Initial Phase 2 Clinical Data for SY-1425
in Fourth Quarter of 2017

Company Also Details SY-1365 Phase 1 Clinical Trial Design

CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company
pioneering the discovery and development of medicines to control the
expression of disease-driving genes, today announced that
pharmacokinetic (PK) and pharmacodynamic (PD) data from the ongoing
Phase 2 clinical trial of SY-1425, its first-in-class selective retinoic
acid receptor alpha (RARα) agonist, in genomically defined subsets of
patients with acute myeloid leukemia (AML) and myelodysplastic syndrome
(MDS), were presented at the European Society of Medical Oncology (ESMO)
2017 Congress in Madrid. Syros also presented the design of its ongoing
Phase 1 clinical trial for SY-1365, a first-in-class selective
cyclin-dependent kinase 7 (CDK7) inhibitor, in patients with advanced
solid tumors.

“The PK and PD data we have seen to date from the ongoing Phase 2
clinical trial show that the dosing regimen of SY-1425 is achieving the
intended drug exposure and eliciting a robust PD response with evidence
of RARα target engagement,” said David A. Roth, M.D., Chief Medical
Officer of Syros. “Importantly, SY-1425 showed favorable PK with
continuous daily dosing, in contrast to historical experience with ATRA,
a non-selective retinoic acid receptor agonist.”

PK and PD Data from Ongoing Phase 2 Clinical Trial of SY-1425

Syros presented data based on an evaluation of 45 AML and MDS patients
from the Company’s ongoing Phase 2 clinical trial, including 36 patients
evaluable for PK and 39 patients evaluable for PD. The data demonstrated
that the dosing regimen being used in the clinical trial achieves blood
levels sufficient to elicit a PD response with evidence of RARα target
engagement in patients who are positive for either the Company’s RARA
or IRF8 biomarkers, or both. The data showed:

Drug exposures consistent with those seen in patients with acute
promyelocytic leukemia (APL). SY-1425 is approved to treat relapsed or
refractory APL in Japan as Amnolake® (tamibarotene) and has
a well-established safety and efficacy profile in APL. The dosing
regimen being used in the Phase 2 trial in RARA or IRF8
biomarker-positive AML and MDS patients is the same as the dose
approved in Japan for APL.

No significant accumulation or reduction in SY-1425 exposure after two
weeks of continuous dosing, demonstrating favorable PK properties in
comparison to historical data with ATRA.

Evidence of RARα target engagement, as measured by robust and
sustained induction of DHRS3 in the majority of patients
evaluated. In preclinical studies, DHRS3 was one of the most
strongly induced genes in response to treatment with SY-1425, leading
to the identification of DHRS3 induction as a PD marker for use
in the trial as an early indicator of whether SY-1425 is affecting the
targeted biology.

Similar induction of DHRS3 across patients with relapsed or
refractory AML, relapsed or refractory higher-risk MDS and lower-risk
transfusion-dependent MDS.

Similar induction of DHRS3 across patients positive for either
the RARA or IRF8 biomarkers, or both.

The Phase 2 clinical trial is assessing the safety and efficacy of
SY-1425 as a monotherapy in four AML and MDS patient populations, as
well as in combination with azacitidine, a standard-of-care therapy, in
newly diagnosed AML patients who are not suitable candidates for
standard chemotherapy. All patients enrolled in the trial are
prospectively selected using the Company’s RARA or IRF8
biomarkers. Additional details about the trial can be found using the
identifier NCT02807558 at www.clinicaltrials.gov.
Syros remains on track to present initial clinical data from the trial
in the fourth quarter of 2017.

In a separate presentation, Syros detailed the design of its ongoing
Phase 1 clinical trial of SY-1365 in patients with advanced solid
tumors, including transcriptionally dependent cancers such as triple
negative breast, small cell lung and ovarian cancers. The multi-center,
open-label trial is expected to enroll approximately 70 patients. The
primary objective of the trial is to assess the safety and tolerability
of escalating doses of SY-1365, with the goal of establishing a maximum
tolerated dose and a recommended Phase 2 dose (RP2D) and regimen. The
dose-escalation phase is open to solid tumor patients for whom standard
curative or palliative measures do not exist or are no longer effective.
Following the dose-escalation phase, an expansion cohort is planned to
further evaluate the safety and anti-tumor activity of SY-1365 in
patients with triple negative breast, small cell lung and ovarian
cancers, and to enroll patients with tumors of any histology in a cohort
focused on analyzing biopsied tumor tissue. SY-1365 target engagement in
peripheral blood mononuclear cells and available tumor biopsies will be
assessed by measuring CDK7 occupancy over the course of treatment.
Additional details about the trial can be found using the identifier
NCT03134638 at www.clinicaltrials.gov.

About Syros Pharmaceuticals

Syros Pharmaceuticals is pioneering the understanding of the non-coding
region of the genome to advance a new wave of medicines that control
expression of disease-driving genes. Syros has built a proprietary
platform that is designed to systematically and efficiently analyze this
unexploited region of DNA in human disease tissue to identify and drug
novel targets linked to genomically defined patient populations. Because
gene expression is fundamental to the function of all cells, Syros’ gene
control platform has broad potential to create medicines that achieve
profound and durable benefit across a range of diseases. Syros is
currently focused on cancer and immune-mediated diseases and is
advancing a growing pipeline of gene control medicines. Syros’ lead drug
candidates are SY-1425, a selective RARα agonist in a Phase 2 clinical
trial for genomically defined subsets of patients with acute myeloid
leukemia and myelodysplastic syndrome, and SY-1365, a selective CDK7
inhibitor in a Phase 1 clinical trial for patients with advanced solid
tumors, including transcriptionally dependent cancers such as triple
negative breast, small cell lung and ovarian cancers. Led by a team with
deep experience in drug discovery, development and commercialization,
Syros is located in Cambridge, Mass.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995,
including without limitation statements regarding the therapeutic
benefit of SY-1425 as a single agent and in combination with
azacitidine; the reporting of initial clinical data from the ongoing
Phase 2 clinical trial of SY-1425 in the fourth quarter of 2017; the
ability to identify an appropriate dose and schedule to support
expansion of the Phase 1 clinical trial of SY-1365, and the benefits of
Syros’ gene control platform. The words ‘‘anticipate,’’ ‘‘believe,’’
‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’
‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’
‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify
forward-looking statements, although not all forward-looking statements
contain these identifying words. Moreover, there can be no assurance
that the PK and PD data generated to date in the ongoing Phase 2
clinical trial of SY-1425 are predictive of the ability of such trial to
meet any of its endpoints. Actual results or events could differ
materially from the plans, intentions and expectations disclosed in
these forward-looking statements as a result of various important
factors, including Syros’ ability to: advance the development of its
programs, including SY-1425 and SY-1365, under the timelines it projects
in current and future clinical trials; demonstrate in any current and
future clinical trials the requisite safety, efficacy and combinability
of its drug candidates; replicate scientific and non-clinical data in
clinical trials; successfully develop a companion diagnostic test to
identify patients with the RARA and IRF8 biomarkers;
obtain and maintain patent protection for its drug candidates and the
freedom to operate under third party intellectual property; obtain and
maintain necessary regulatory approvals; identify, enter into and
maintain collaboration agreements with third parties; manage
competition; manage expenses; raise the substantial additional capital
needed to achieve its business objectives; attract and retain qualified
personnel; and successfully execute on its business strategies; risks
described under the caption “Risk Factors” in Syros’ Quarterly Report on
Form 10-Q for the quarter ended June 30, 2017, which is on file with the
Securities and Exchange Commission; and risks described in other filings
that Syros makes with the Securities and Exchange Commission in the
future. Any forward-looking statements contained in this press release
speak only as of the date hereof, and Syros expressly disclaims any
obligation to update any forward-looking statements, whether because of
new information, future events or otherwise.